Intraocular radiotherapy treatment for macular degeneration

ABSTRACT

A surgical device for localized delivery of beta radiation in surgical procedures, particularly ophthalmic procedures. Preferred surgical devices include a cannula with a beta radiotherapy emitting material at the distal end of the cannula. The surgical device is particularly suitable for use in the treatment of treat Age Related Macular Degeneration (AMD).

This application is a continuation of co-pending U.S. application Ser.No. 11/075,098, filed on Mar. 8, 2005, which is a continuation of U.S.application Ser. No. 09/790,486 filed on Feb. 22, 2201, now U.S. Pat.No. 6,875,165.

The present invention relates to a device and method for localizeddelivery of beta radiation in surgical procedures, particularlyophthalmic procedures. More particularly, the present invention relatesto a device and method for localized delivery of beta radiation to treatAge Related Macular Degeneration (AMD)

BACKGROUND

The slow, progressive loss of central vision is known as maculardegeneration. Macular degeneration affects the macula, a small portionof the retina. The retina is a fine layer of light-sensing nerve cellsthat covers the inside back portion of the eye. The macula is thecentral, posterior part of the retina and contains the largestconcentration of photoreceptors. The macula is typically 5 to 6 mm indiameter, and its central portion is known as the fovea. While all partsof the retina contribute to sight, only the macula provides the sharp,central vision that is required to see objects clearly and for dailyactivities including reading and driving.

Macular degeneration is generally caused by age (Age Related MacularDegeneration, “AMD”) or poor circulation in the eyes. Smokers andindividuals with circulatory problems have an increased risk fordeveloping the condition.

AMD is the leading cause of blindness in people older than 50 years indeveloped countries. Between the ages of 52-64 approximately 2% of thepopulation are affected. This rises to an astounding 28% over the age of75.

The two forms of macular degeneration are known as “wet” and “dry”macular degeneration.

Dry macular degeneration blurs the central vision slowly over time.Individuals with this form of macular degeneration may experience adimming or distortion of vision that is particularly noticeable whentrying to read. In dry macular degeneration, yellowish deposits calleddrusen develop beneath the macula. Drusen are accumulations of fattydeposits, and most individuals older than 50 years have at least onesmall druse. These fatty deposits are usually carried away by bloodvessels that transport nutrients to the retina. However, this process isdiminished in macular degeneration and the deposits build up. Drymacular degeneration may also result when the layer of light-sensitivecells in the macula becomes thinner as cells break down over time.Generally, a person with dry form macular degeneration in one eyeeventually develops visual problems in both eyes. However, dry maculardegeneration rarely causes total loss of reading vision.

Wet macular degeneration (the neovascular form of the disease) is moresevere than dry macular degeneration. The loss of vision due to wetmacular degeneration also comes much more quickly than dry maculardegeneration. In this form of the disease, unwanted new blood vesselsgrow beneath the macula (Choroidal Neo-Vascularization (CNV) endothelialcells). These choroidal blood vessels are fragile and leak fluid andblood, which causes separation of tissues and damages light sensitivecells in the retina. Individuals with this form of macular degenerationtypically experience noticeable distortion of vision such as, forexample, seeing straight lines as wavy, and seeing blank spots in theirfield of vision. Early diagnosis of this form of macular degeneration isvital. If the leakage and bleeding from the choroidal blood vessels isallowed to continue, much of the nerve tissue in the macula may bekilled or damaged, and such damage cannot be repaired because the nervecells of the macula do not grow back once they have been destroyed.While wet AMD comprises only about 20% of the total AMD cases, it isresponsible for approximately 90% of vision loss attributable to AMD.

Currently, Photo-Dynamic Therapy (PDT) is used to treat individuals withwet macular degeneration. During PDT, a photo-sensitive drug is firstdelivered to the patient's system, typically by injecting the drug intothe patient's bloodstream through a vein. The photo-sensitive drugattaches to molecules in the blood called lipoproteins. Because thechoroidal blood vessels require a greater amount of lipoproteins thannormal vessels, the drug is delivered more quickly and in higherconcentrations to the choroidal blood vessels. Next, a non-thermal diodelaser light is aimed into the eye to activate the photo-sensitive drug.The activated drug subsequently causes the conversion of normal oxygenfound in tissue to a highly energized form called “singlet oxygen.” Thesinglet oxygen, in turn, causes cell death by disrupting normal cellularfunctions, resulting in the closure of the choroidal blood vessels whileleaving normal vessels still functional. While PDT cannot restorevision, it reduces the risk of vision loss by restricting the growth ofabnormal choroidal blood vessels.

Laser therapy (“Laser Photocoagulation”), as opposed to Photo-DynamicTherapy (PDT), uses heat. Basically, a “hot” laser is aimed at thechoroidal blood vessels, resulting in the formation of heat when thelaser contacts the vessels. This stops the growth, leakage, and bleedingof the choroidal blood vessels. However, the laser destroys surroundinghealthy tissue in the process (collateral damage). Further, the “hot”laser forms scars, which may cause blind spots.

PDT, thus, is particularly advantageous because it does not use heat, soless collateral damage results, and the procedure can be repeated asmany times as necessary. However, while PDT has shown some efficacy, thepopulation of patients in which it shows efficacy is small (less than20%). Furthermore, PDT does not typically restore lost vision, butrather, only slows the progression of vision loss. In the attempt todesign a selective disruption therapy, it appears that PDT, althoughgroundbreaking, is not aggressive enough to provide satisfying resultsfor affected patients.

Radiation is a promising medical technology that may be effective forthe treatment of choroidal neovascularization due to age related maculardegeneration. There are basically three types of nuclear radiation:Alpha, Beta, and Gamma.

An alpha particle is simply a helium nucleus. It has the lowest power,penetration, and danger associated with it of the three types ofradiation. Several sheets of paper would serve as a shield against alpharadiation.

Gamma radiation is the most powerful, most penetrating, and mostdangerous type of radiation. Gamma radiation is an energy wave, not justa particle. Gamma sources are photons. Several meters of rock or manycentimeters of lead are required to shield gamma radiation.

Gamma radiotherapy has been shown to be effective in vascular radiationtherapy, particularly for the treatment of in-stent restenosis.Randomized data from the Scripps Trial (The SCRIPPS Trial—Catheter-BasedRadiotherapy to Inhibit Coronary Restenosis; J Invas Cardiol12(6):330-332 (2000)) a randomized, double blind, placebo-controlledstudy demonstrated a reduction in restenosis rates from 54% in theplacebo group to 17% in patients treated with gamma radiation (¹⁹²Ir).Gamma sources penetrate human tissues deeply. This makes gamma energyideal for treating large vessels. Gamma sources have been used in theclinical arena for decades and hospital radiotherapy departments havesignificant years of experiences using gamma sources.

There are, however, numerous disadvantages to using gamma sources.Photons are not blocked by the “usual” lead shields. A 1 inch leadshield is required. This is usually provided in the form of a verycumbersome heavy lead device attached to rollers that allow it to bewheeled into the catheterization laboratory. Due to the presence ofdeeply penetrating ionizing radiation, when high-energy gamma radiationis used in the catheterization laboratory, the procedure room must becleared of all “nonessential” personnel. The patient is observed from a“control room” which is protected by lead shielding. Also, the patientreceives more radiation from a gamma radiation procedure as compared toother radiation procedures. The radiation oncologist, who delivers theactual radiation sources, also receives additional radiation exposure.This problem of radiation exposure in the catheterization laboratoryenvironment limits the maximal specific activity of the radiationsources. If the sources are of very high activity, the exposure tohealth care personnel in the control room will be higher than backgroundexposure. This would be unacceptable. To circumvent this problem, lowerspecific activity sources must be used. This requires a long dwell time(8 to 20 minutes) to achieve therapeutic doses.

SUMMARY OF THE INVENTION

The present invention provides new surgical devices and methods for usethereof. Devices and methods of the invention are particularly usefulfor treatment of eye disorders such as Age Related Macular Degeneration.

More particularly, the present invention provides a device for localizeddelivery of beta radiation during surgical procedures and methods of usethereof. The device is particularly suitable for the localized deliveryof beta radiation for the treatment of macular degeneration. The devicedelivers beta radiation to the affected sub-macular region afflictedwith the condition.

Beta radiation is a high-speed electron. A typical source of betaradiation may be, for example, radioisotope Phosphorus 32 (³²P). Betasource electrons only penetrate 1 to 2 mm into human tissue. Even thickplastics easily shield beta energy. The fact that exposure from betasources is limited allows the specific activity to be much higher thanthat of gamma sources. This translates into very short dwell times, forexample, approximately 3 to 8 minutes of exposure is estimated forophthalmic applications using a beta source, as opposed to the longerlong dwell time associated with the use of a gamma source (8 to 20minutes). Radiation safety concerns surrounding the use of beta sourcesare vastly reduced compared to that of gamma radiation. Health carepersonnel are able to remain in the operating room and additionalexposure to the patient and surgeon is negligible. The dose of betaradiation received during macular radiotherapy will be less than thatreceived during a conventional chest x-ray. We have found that betaradiotherapy can be an optimal balance of power, penetration, and safetyfor many medical applications and specifically for the treatment ofchoroidal neo-vascularization (CNV) caused by AMD and other diseases ofthe eye.

In particular, we believe that the exposure of the new blood vesselsformed during wet type macular degeneration to the beta radiationprovides sufficient disruption of the cellular structures of the newblood cell lesions to reverse, prevent, or minimize the progression ofthe macular degeneration disease process. Such therapy in accordancewith the invention can potentially restore visual acuity, extendretention of visual acuity, or slow the progressive loss of visualacuity.

In a preferred embodiment, the surgical device includes a radiotherapyemitting material positioned on the device, such as a cannula, typicallya distal end or portion of the cannula. For added safety, theradiotherapy emitting material is preferably shielded. The cannula maybe straight or curved. Preferably, to provide access to the macula froma retinotomy peripheral to the macula, the cannula preferably has a bendor curve. Preferably, the beta radiotherapy emitting material is housedin and partially shielded in the distal end of the cannula by a thinwall metal, such as stainless steel, and/or by a thin wall polymer,plastic, or similar material. The shield may also be designed to beretracted to provide a pathway during the exposure period.

The cannula may have a handle extending its proximal end for providingthe surgeon with a better grip on the device and for allowing thesurgeon to easily reach the surgical site.

The radiotherapy emitting material preferably emits purely betaradiation, however, the radiotherapy emitting material may also be amaterial that emits very low and insignificant doses of gamma radiationin addition to beta radiation. Any conventional beta radiation emittingmaterials used in surgical settings may be used in the present device.For example, some suitable pure beta radiation emitting materials mayinclude: ²⁰⁶Tl (half-life of about 4.20 min), ^(60m)Co (half-life ofabout 10.47 min), ⁶⁹Zn (half-life of about 55.6 min), ²⁰Pb (half-life ofabout 3.253 hours), ¹⁴³Pr (half-life of about 13.58 days), ³²P(half-life of about 14.282 days), ³³P (half-life of about 25.34 days),⁴⁵Ca (a half-life of about 165 days), ⁹⁰Sr (half-life of about 28.5years), ⁹⁹Te (half-life of about 2.13×10⁵ years) and ³⁶S (half-life ofabout 3.08×10⁵ years).

The duration of radiation emission required during a single treatmentfor Age Related Macular Degeneration using the device can be quiteshort, e.g. less than 10 or 15 minutes, or even less than 5 minutes.Typical treatments will range from about 1 to 15 minutes, more typically2 to ten minutes. Thus, for a single-use device, it is possible to usebeta radiation emitting materials having short half-lives. However, insome cases, it is desirable to provide a device with a long shelf-lifeif, for example, the device is not immediately used or if the device isreusable. Thus, in some cases, it is preferred that the beta radiationemitting material is selected from materials that have a half-life of atleast about 2 years. Further, when used for the treatment of Age RelatedMacular Degeneration, it is preferable that the beta emitting materialis selected from materials having an energy ranging from about 50cGr/sec to about 100 cGr/sec.

The present invention also provides device kits, which preferablycomprise one or more of the described beta radiotherapy emittingsurgical devices, preferably packaged in sterile condition.

Other aspects and embodiments of the invention are discussed infra.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an isometric view of one embodiment of the surgical device inaccordance with the present invention.

FIG. 2 shows a diagram of a normal, healthy eye.

DETAILED DESCRIPTION OF THE INVENTION

Referring now to the various figures of the drawing, wherein likereference characters refer to like parts, there is shown in FIG. 1 aview of a surgical device 1 in accordance with the invention.

In a preferred embodiment, the surgical device 1 includes a cannula 2,having a proximal end 4 and a distal end 6. Cannulas are well known and,thus, although described below with reference to a preferred embodiment,the general features (e.g. size, shape, materials) of the cannula 2 maybe in accordance with conventional cannulas.

A radiotherapy emitting material 8 is located at the distal end 6 of acannula 2. The radiotherapy emitting material 8 preferably emits purebeta radiation because beta radiation is easily blocked and, if notshielded, does not penetrate more than about 1-2 mm in human tissue.However, it is possible to use a radiotherapy emitting material 8 thatemits very low and insignificant doses of gamma radiation in addition tobeta radiation. For example, some suitable pure beta radiation emittingmaterials may include: ²⁰⁶Tl (half-life of about 4.20 min), ^(60m)Co(half-life of about 10.47 min), ⁶⁹Zn (half-life of about 55.6 min), Pb(half-life of about 3.253 hours), ¹⁴³Pr (half-life of about 13.58 days),³²P (half-life of about 14.282 days), ³³P (half-life of about 25.34days), ⁴⁵Ca (half-life of about 165 days), ⁹⁰Sr (half-life of about 28.5years), ⁹⁹Te (half-life of about 2.13×10⁵ years), 36S (half-life ofabout 3.08×10⁵ years).

The half-life of the beta emitting material may vary depending on theuse of the device. For example, when used to treat Age Related MacularDegeneration (AMD), one treatment using the device will typicallyrequire radiation emission for a period of time ranging from about twoto about ten minutes. Thus, single-use devices that are disposed ofbetween treatments may be fabricated using radiotherapy emittingmaterials 8 with a relatively short half-life. In some circumstances, itis preferable to provide a device having a long shelf-life. In suchcircumstances, it is preferable to fabricate the device usingradiotherapy emitting materials 8 that are continuously active for avery long time (e.g. with a half-life of at least 2 years).

The energy of the beta emitting material may vary depending on the useof the device. For example, when used to treat Age Related MacularDegeneration (AMD), the beta emitting material is preferably selectedfrom materials having an energy ranging from about 50 cGr/sec to about100 cGr/sec.

Preferably, for added safety during use of the surgical device 1, theradiotherapy emitting material 8 is at least partially shielded. Becausebeta radiation is easily shielded, the radiotherapy emitting material 8may be housed in and partially shielded in, for example, a thin wallmetal, such as stainless steel, or by a thin wall polymer, plastic, orsimilar material. This may be accomplished by providing a thin wall orshield 10 at the distal end 6 of the cannula 2 about the radiotherapyemitting material 8. In one embodiment, at least a portion of theradiotherapy emitting material 8 is housed in and partially shielded inthe distal end 6 of the cannula 2. Thus, at least a portion of thedistal end 6 of the cannula 2 is fabricated of, for example, a thin wallmetal, such as stainless steel, or by a thin wall polymer, plastic, orsimilar material. Alternatively, if desired, the entire cannula 2 may befabricated of a thin wall metal, such as stainless steel or similarmaterial, or by a thin wall polymer, plastic, or similar material. Theshield 10 may also be designed to be retractable to provide further easein handling the device and shielding of the radiotherapy emittingmaterial 8 when desired.

To provide a surgeon, patient and others in the operating area withadequate protection from the beta radiation, the thickness of the wallor shield 10 or the thickness of the distal end 6 of the cannula inwhich the radiotherapy emitting material 8 is housed preferably rangesfrom about 0.5 to about 3 mm, and more preferably, from about 1 mm toabout 2 mm. While thicknesses above about 3 mm may be used, it isbelieved that thicknesses above about 3 mm will not provide significantadditional protection from the beta radiation and would make thesurgical device 1 bulky and more difficult to handle.

The cannula 2 may have a handle 14 extending its proximal end 4 forproviding the surgeon with a better grip on the surgical device 1 andfor allowing the surgeon to easily reach the surgical site. Such handlesare known and, thus, the handle 14 of the present invention may be inaccordance with conventional handles. The handle may be attached to thecannula 2 by a frictional fit and/or conventional fastening means. Theconnecting means, such as a hub 16 portion may further be included anddesigned so as to assist in connecting the cannula 2 to the handle 14via a frictional fit and, if desired, conventional fastening means maybe used to assist the hub 16 in connecting the cannula 2 to the handle14.

In use, the surgical device 1 is gripped by the handle 14 or a portionof the proximal end 4 of the cannula 2, and the distal end 6 of thecannula 2 with the radiotherapy emitting material 8 is introduced intothe surgical site. In contrast to prior methods in which access to themacula is provided by inserting devices between the eyelid and sclera,the present procedure involves making a standard vitrectomy portincision (typically about a 20 gage—approximately 0.89 mm—incision) inthe eye to provide access to the macula, located at the back of the eye.The distal end 6 of the cannula 2 and the radiotherapy emitting material8 are then inserted through the incision towards the macula. Thisapproach will provide the surgeon with a superior ability to locate theradiotherapy emitting material directly in the affected area. Thissuperior positioning approach provides for more effective therapy andenhanced safety for the lens and optic disc. The surgeon will thenperform a vitrectomy and pre-detach the macula by injecting salinebeneath the retina with a 41 gage needle to gain “direct access” to thesub macular membrane.

The radiotherapy emitting material 8 is preferably positioned withinabout 1 mm to about 3 mm of the choroidal blood vessels being treated.In some cases, however, the tip may be placed directly on the choroidalblood vessels.

During the procedure, the surgeon can view the interior of the eye usinga standard procedure for viewing the macula through the cornea with anilluminated operating microscope and a lens placed on the cornea. Thesurgeon can alternatively view the interior of the eye by making asecond 20 gage incision to provide access for a fiber optic illuminator,which is a standard practice in retinal surgery.

The cannula 2 is preferably elongate in shape to provide easy access tothe surgical site. Preferably, the body portion is designed so as toconform with the incision made in the eye, such that as the cannula 2 isinserted in the eye through the incision, the incision molds around thebody portion and prevents leakage around the cannula 2. Further, thecannula 2 is preferably designed with a smooth surface so as to preventfurther trauma to the eye as it is entered through the incision. In onepreferred embodiment, as shown in FIG. 1, the cannula 2 has an elongatecylindrical shape. The cannula 2 may have a substantially uniform crosssectional diameter or may taper. In one preferred embodiment, thecannula 2 tapers towards the distal end 6 to provide precision inplacement of the radiotherapy emitting material 8 and to allow fortargeted treatment of only the defective, leaking vessels. Although thecannula 2 is depicted as cylindrical in shape, other shapes may be usedas desired. Additionally, the cannula 2 may include a bend to provideenhanced access to areas that are difficult to reach. Preferably, toprovide access to the macula from a retinotomy peripheral to the macula,the cannula preferably has a curve.

The dimensions of the surgical device 1 may vary depending on itsultimate use. For example, to treat AMD, in cases where the cannula 2 isinserted into the eye through an incision, the length of the cannula 2would be designed so that the radiotherapy emitting material 8 wouldreach the appropriate distance to the back of the eye while allowingonly the cannula 2, and not the hub 16, handle 14 or other apparatusconnected to the proximal end 6 of the cannula 2, to enter the incision.As such, the portion of the cannula that enters the incision in the eyepreferably has a length ranging from about 28 mm to about 32 mm. Theradiotherapy emitting material 8 portion of the device preferably has alength that ranges from about 2 mm to about 6 mm. More preferably, thelength of the radiotherapy emitting material 8 portion of the deviceranges from about 2 mm to about 3 mm. The handle 14 of the devicepreferably ranges from about 3-6 inches to provide a suitable grippingmeans for the surgeon. If included, the hub 16, which connects thecannula 2 to the handle 14, preferably has a length ranging from about10 mm to about 12 mm. Further, in applications where a portion of thecannula 2 is inserted into the eye through an incision, the diameter orthickness of the cannula 2 preferably conforms to the size of theincision so that the incision molds around the cannula 2 and preventsleakage around the cannula 2. For example, in preferred embodiments, thediameter or thickness of the cannula 2 ranges from about 0.6 mm to about1.2 mm. More preferably, the diameter or thickness of the cannula 2ranges from about 0.8 mm to about 1.0 mm. However, it is to beunderstood that the diameter or thickness of the cannula 2 and thelength of the portion of the cannula 2 that enters the incision may varydepending on the particular procedure performed, the size of theincision made and the distance from the incision to the treatment area.

The cannula 2 may be fabricated of any conventional materials used informing similar surgical devices. Preferably, the material islightweight and strong. Some conventional materials are plastics andstainless steel. Further, because the cannula 2 is inserted in the eyearea in some applications, the materials used in forming the cannula 2must be medically approved for such contact.

The radiotherapy emitting material 8 may be fixedly or removablyconnected to the distal end 6 of the cannula 2. Known means such as, forexample, adhesives may be used to fixedly secure the radiotherapyemitting material 8 to the cannula 2. The radiotherapy emitting material8 may also be removably connected to the cannula 2 by known means suchas, for example, forming the radiotherapy emitting material 8 and thecannula 2 to have corresponding threaded portions that allows removableattachment of the radiotherapy emitting material 8 to the cannula 2 sothat the device may be reused by simply sterilizing the cannula 2 withethylene oxide gas or similar means, and replacing the radiotherapyemitting material 8. Preferably, the entire surgical device 1 isdisposed of and replaced between uses to maintain sterility and preventcross-contamination between uses.

The present invention also includes kits that comprise one or more betaradiotherapy emitting surgical devices of the invention, preferablypackaged in sterile condition. Kits of the invention may also includewritten instructions for use of the beta radiotherapy emitting surgicaldevices and other components of the kit.

The foregoing description of the invention is merely illustrativethereof, and it is understood that variations and modifications can beeffected without departing from the scope or spirit of the invention asset forth in the following claims. For example, although the presentinvention is described in detail in connection with ophthalmic surgicalprocedures, particularly in connection with the treatment of AMD, thepresent invention is not limited to use on the eye. Rather, the presentinvention may be used on other areas of the body to treat variousconditions such as, for example, the prevention of restenosis.

1-42. (canceled)
 43. A method for treating macular degeneration in thehuman eye, comprising: inserting an ionizing radiation source into theeye; positioning the ionizing radiation source at a distance of about 1mm to about 3 mm from subretinal tissue associated with maculardegeneration; and exposing the subretinal tissue to radiation emittedfrom the ionizing radiation source.
 44. The method in accordance withclaim 43 in which the subretinal tissue comprises tissue of thesub-macular region.
 45. The method in accordance with claim 43 in whichthe subretinal tissue comprises blood vessels.
 46. The method inaccordance with claim 43 in which the subretinal tissue is exposed to atherapeutically effective amount of radiation to treatneovascularization.
 47. The method in accordance with claim 43 in whichthe subretinal tissue is exposed to radiation for a time period betweenabout 1 minute and about 15 minutes.
 48. The method in accordance withclaim 43 in which the ionizing radiation source has an energy sufficientto provide a dose rate of about 50 cGy/sec to about 100 cGy/sec.
 49. Themethod in accordance with claim 43 in which the radiation emitted fromthe ionizing radiation source comprises beta radiation.
 50. The methodin accordance with claim 43 in which the exposing comprises targetingthe radiation only at selected subretinal tissue.
 51. A method ofradiotherapy for macular degeneration, comprising: inserting into theeye an ionizing radiation source having an energy sufficient to providea dose rate of about 50 cGy/sec to about 100 cGy/sec; and exposingsubretinal tissue to a radiation emitted from the ionizing radiationsource.
 52. The method in accordance with claim 51 in which thesubretinal tissue comprises blood vessels.
 53. The method in accordancewith claim 51 in which the exposing comprises exposing the subretinaltissue for a time period sufficient to treat neovascularization.
 54. Themethod in accordance with claim 51 in which the exposing comprisesexposing the subretinal tissue to the radiation for a time periodbetween about 1 minute and about 15 minutes.
 55. The method inaccordance with claim 51 in which the radiation emitted from theionizing radiation source comprises beta radiation.
 56. The method inaccordance with claim 51 in which the exposing comprises targeting theradiation only at selected subretinal tissue.
 57. The method inaccordance with claim 56 in which the selected tissue comprises bloodvessels.
 58. The method in accordance with claim 51 in which theexposing comprises exposing the subretinal tissue to a therapeuticallyeffective amount of radiation sufficient to treat neovascularization.59. A method for treating macular degeneration, comprising: inserting anionizing radiation source into the eye; positioning the ionizingradiation source about 1 mm to about 3 mm from subretinal choroidalblood vessels, the ionizing radiation source having an energy sufficientto provide a dose rate of about 50 cGy/sec to about 100 cGy/sec.; andexposing the choroidal blood vessels to a therapeutically effectiveamount of radiation emitted from the ionizing radiation source to treatneovascularization.
 60. The method in accordance with claim 59 in whichthe choroidal blood vessels are exposed to radiation for a time periodbetween about 1 minute and about 15 minutes.
 61. The method inaccordance with claim 59 in which the radiation emitted from theionizing radiation source comprises beta radiation.
 62. The method inaccordance with claim 59 in which the exposing comprises targeting theradiation only at defective choroidal blood vessels.